There have been documented instances in the art of passively immunizing neonates against infection with a selected disease-causing agent by administering a vaccine to a pregnant animal or to a nursing mother. These passive immune responses are believed to be due to the transfer of maternal IgA antibodies through the placenta to the infant and/or by intestinal absorption of maternal immunoglobulins present in the colostrum or milk by the neonate.
Colostrum and milk, which provide protective immune factors to the neonate, also have an extraordinary and unique combination of carbohydrates, fats, amino acids, minerals, vitamins, growth promoting factors such as epidermal-growth factor, insulin, and somatomedins, as well as lactoferrin, interleukin-1 (IL-1) and vasoactive intestinal peptides and some neuropeptides.
After ingestion of colostrum, maternal immune factor, especially antibodies, antibody producing cells, and T cells are seeded via intestinal mucosal tissue and maintained in various lymphoid tissues of the neonate during the early post-natal period of maturation of its immune system until the infant's own lymphoid system is capable of antibody production and induction or priming of T cells. Human colostrum and milk contain activated and memory T lymphocytes up to 73% of the total lymphocyte population. Memory T lymphocytes make up to 92% of the total lymphocyte population. Furthermore, experimental data on human colostrum and milk suggest that virtually all (99.8%) of T cells of the helper phenotype (CD.sup.4+), and most (92%) of the T cells of cytotoxic/suppressor phenotype (CD.sup.8+) are memory T cells. These T lymphocytes, in collaboration with other immune factors, play an important role in the immunological development of the neonate with respect to its ability to respond to future encounters with environmental antigens or deliberate exposure via vaccinations.
In the art of immunology it is well established that exposure of neonatal animals to a majority of environmental antigens or vaccination usually results in tolerance induction depending on various factors, such as type of antigen, dose and route of administration and genetic background. In contrast, a similar exposure of the adults would invariably result in an immune response.
The cellular basis of this disparate responsiveness of neonates and adults is not clearly defined. This phenomenon may be attributed to two critical factors, namely, status of maternal immune reactivity and maternal B and T cell repertoire, and the post-natal antigen exposure of the neonate by gram negative microbes (LPS). For example, colonization of the gut occurs rapidly after birth, e.g., in calves about 4 days, and in pigs about 1 week.
There exists a need in the vaccine art for a method of enhancing immunity, particularly non-antibody mediated immunity (or cell mediated immunity), in neonates lacking fully developed immune systems.